October 23, 2023
2 minute read
Important points:
- Sotorasib and panitumumab prolonged PFS compared to standard of care.
- Grade 3 or higher adverse events occurred less frequently with the combination.
MADRID — Sotorasib and panitumumab prolonged PFS compared to standard treatment in chemotherapy-resistant patients KRAS G12C mutations in metastatic colorectal cancer, study results presented at the ESMO conference showed.
The combination also provided benefits in terms of response rate, duration of response, and disease control, according to study results published at the same time. New England Medical Journal.
KRAS G12C mutations are present in 3% to 4% of metastatic colorectal cancers. Based on the research background, monotherapy with KRAS G12C inhibitors has demonstrated only modest efficacy.
Dr. Filippo Pietrantonio, Gastrointestinal medical oncologists at the Fondazione IRCCS Istituto Nazionale dei Tumori in Italy conducted the randomized phase 3 CodeBreaK trial to evaluate the use of sotorasib (Lumakras, Amgen) in combination. class Panitumumab (Vectibix, Amgen), a G12C inhibitor and fully human monoclonal anti-EGFR antibody, may improve outcomes.
The multicenter, open-label study included 160 patients with chemotherapy-resistant metastatic colorectal cancer who had not received prior drug therapy. class G12C inhibitor.
Researchers randomly assigned 53 patients to receive sotorasib 960 mg/day and panitumumab 6 mg/kg intravenously. 53 patients received sotorasib 240 mg daily and panitumumab 6 mg/kg IV. Fifty-four patients received investigator’s choice of either trifluridine-tipiracil (Lonsurf; Taiho Oncology, Servier) or regorafenib (Stivarga, Bayer).
PFS by blinded independent central review served as the primary endpoint. Key secondary endpoints include OS, objective response, and disease control rate.
Median follow-up was 7.8 months (range, 0.1-13.9 months).
The study met its primary endpoint, as the combination of both sotorasib and panitumumab resulted in significant PFS improvements compared to standard care (sotorasib 960 mg, HR = 0.49; 95% CI, 0.3-0.8; sotorasib 240 mg, HR = 0.58; 95% CI, 0.36-0.93).
At the time of data cutoff, OS data remained immature.
Researchers reported that median PFS was longer in both the sotorasib and panitumumab groups (sotorasib 960 mg, 5.6 months; sotorasib 240 mg, 3.9 months; standard care, 2.2 months).
Results also showed higher ORR (sotorasib 960 mg, 26.4%; sotorasib 240 mg, 5.7%, standard of care, 0%) and higher disease control rates (sotorasib 960 mg, 71.7%; sotorasib 240 mg, 67.9%, standard treatment, 46.3%).
Median duration of response was 4.4 months in the sotorasib 960 group but not reached in the sotorasib 240 mg group.
Grade 3 or higher treatment-related adverse events occurred in 35.8% of patients in the sotorasib 960 mg group, 30.2% of patients in the sotorasib 240 mg group, and 43.1% of patients in the standard treatment group.
Grade 3 or higher treatment-related events reported in patients in the sotorasib 960 mg group included dermatitis acneiformis (11.3%), hypomagnesemia (5.7%), and rash (5.7%). Ta. Grade 3 or higher treatment-related adverse events observed in the sotorasib 240 mg group included hypomagnesemia (7.5%) and diarrhea (5.7%).
In the standard treatment arm, grade 3 or higher treatment-related adverse events included neutropenia (23.5%), anemia (5.9%), and hypertension (5.9%).
No fatal treatment-related adverse events occurred.
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Pietrantonio F et al. Abstract LBA10. Presented at the European Society of Clinical Oncology Congress. October 20-24, 2023. Madrid.
Disclosure: Pietrantonio reports financial relationships with companies including Amgen, Astellas, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Eli Lilly & Company, Incyte, Merck Serono, and Merck Sharp & Dohme. See the study for all researchers’ relevant financial disclosures.
perspective
Miriam Koopman, MD
CodeBreaK 300 is the first randomized phase 3 trial investigating the efficacy of combination therapy. class G12C inhibition and anti-EGFR Treatment of previously treated metastatic colorectal cancer.
We saw encouraging results with high rates of tumor regression from baseline and a significant benefit in PFS in highly pretreated patients.
Comparable results between the CodeBreaK 300 control arm and a previously published phase 3 study with trifluridine-tipiracil and regorafenib support the validity of the results.
However, since trifluridine tipiracil and bevacizumab (Avastin, Genentech) are the current late-stage standard drugs, it is necessary to compare sotorasib plus panitumumab and trifluridine tipiracil plus bevacizumab for the following patients: class G12C mutant tumor.
OS and quality of life results will determine whether sotorasib plus panitumumab is the final standard of care for patients who: class G12C mutation disease. If positive, this combination should only be used in patients who meet the CodeBreaK eligibility criteria, and as only 3% of patients overall have performance status 2, further data on this subset of patients is needed.
Other first- and second-line studies combining RAS inhibitors and anti-anti-inflammatory drugsEGFR Chemotherapy is also continuing. Moving to an earlier line of treatment that combines chemotherapy may provide additional benefit to patients.
Miriam Koopman, MD
Utrecht University Medical Center
Disclosure: Koopman reports financial or other relationships with Amgen, Bayer, Bristol-Myers Squibb, GSK, Merck Serono, Servier, Sanofi and other entities.
European Society of Clinical Oncology General Meeting